* Osteopontin mediates tumorigenic transformation of a preneoplastic murine cell line by suppressing anoikis: an Arg-Gly-Asp-dependent-focal adhesion kinase-caspase-8 axis.
- Osteopontin (OPN), an adhesive, matricellular glycoprotein, is a rate-limiting factor in tumor promotion of skin carcinogenesis. With a tumor promotion model, the JB6 Cl41.5a cell line, we have shown that suppressing 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced OPN expression markedly inhibits TPA-induced colony formation in soft agar, an assay indicative of tumorigenic transformation. Further, the addition of exogenous OPN promotes colony formation of these cells. These findings support a function of OPN in mediating TPA-induced neoplastic transformation of JB6 cells. In regard to the mechanism of action by OPN, we hypothesized that, for JB6 cells grown in soft-agar, secreted OPN induced by TPA stimulates cell proliferation and/or prevents anoikis to facilitate TPA-induced colony formation. Analyses of cell cycle and cyclin D1 expression, and direct cell counting of JB6 cells treated with OPN indicate that OPN does not stimulate cell proliferation relative to non-treated controls. Instead, at 24 h, OPN decreases anoikis by 41%, as assessed by annexin V assays. Further, in suspended cells OPN suppresses caspase-8 activation, which is mediated specifically through its RGD-cell binding motif that transduces signals through integrin receptors. Transfection studies with wild-type and mutant focal adhesion kinases (FAK) and Western blot analyses suggest that OPN suppression of caspase-8 activation is mediated through phosphorylation of FAK at Tyr(861). In summary, these studies indicate that induced OPN is a microenvironment modulator that facilitates tumorigenic transformation of JB6 cells by inhibiting anoikis through its RGD-dependent suppression of caspase-8 activity, which is mediated in part through the activation of FAK at Tyr(861).
=>1.さらにずっと, さらに先に, 一層遠く, その上, 更に, もっと遠い, なお一層の, さらに遠く,
もっと先に, いっそうはるかに, さらにまた, さらになお(furthermore), 2.進める, 助成する, 促進する
Overview of verb further
The verb further has 2 senses (first 2 from tagged texts)
1. (7) foster, further -- (promote the growth of; "Foster our children's well-being and education")
2. (2) promote, advance, boost, further, encourage -- (contribute to the progress or growth of; "I
am promoting the use of computers in the classroom")
Overview of adj further
The adj further has 1 sense (first 1 from tagged texts)
1. (2) further, farther -- (more distant in especially degree; "nothing could be further from the
truth"; "further from our expectations"; "farther from the truth"; "farther from our expectations")
Overview of adv further
The adv further has 3 senses (first 3 from tagged texts)
1. (33) further, farther -- (to or at a greater extent or degree or a more advanced stage (`further'
is used more often than `farther' in this abstract sense); "further complicated by uncertainty about
the future"; "let's not discuss it further"; "nothing could be further from the truth"; "they are
further along in their research than we expected"; "the application of the law was extended
farther"; "he is going no farther in his studies")
2. (10) further -- (in addition or furthermore; "if we further suppose"; "stated further that he
would not cooperate with them"; "they are definitely coming; further, they should be here already")
3. (1) farther, further -- (to or at a greater distance in time or space (`farther' is used more
frequently than `further' in this physical sense); "farther north"; "moved farther away"; "farther
down the corridor"; "the practice may go back still farther to the Druids"; "went only three miles
further"; "further in the future")
Overview of adv far
The adv far has 5 senses (first 4 from tagged texts)
1. (61) far -- (to a considerable degree; very much; "a far far better thing that I do"; "felt far
worse than yesterday"; "eyes far too close together")
2. (39) far -- (at or to or from a great distance in space; "he traveled far"; "strayed far from
home"; "sat far away from each other")
3. (22) far -- (at or to a certain point or degree; "I can only go so far before I have to give up";
"how far can we get with this kind of argument?")
4. (3) far -- (remote in time; "if we could see far into the future"; "all that happened far in the
past")
5. far -- (to an advanced stage or point; "a young man who will go very far")
--- WordNet end ---